Jakavi Tablets 15 mg (Ruxolitinib Phosphate)

Adult dose

Administration of this drug should be initiated by a physician experienced in the administration of anticancer agents. This drug is taken orally, with or without food. If a dose is missed, the patient should not take an additional dose of this drug and should take the next prescribed dose. Treatment with this drug may be continued for myelofibrosis and polycythemia vera as long as the benefit-risk ratio remains positive. However, if spleen size has not decreased or symptoms have not improved after 6 months of treatment, treatment with this drug should be discontinued. For patients with graft-versus-host disease who respond to treatment, tapering the dose of this drug may be considered after corticosteroids have been discontinued. It is recommended that the dose of this drug be reduced by 50% every 2 months. If signs or symptoms of graft-versus-host disease recur during or after dose tapering, dose re-escalation should be considered. Blood cell counts: A complete blood count (CBC) must be obtained before starting treatment with this drug. CBCs should also be monitored every 2 weeks ∼ 4 weeks until the dose has stabilized, and thereafter as clinically indicated. Myelofibrosis: The recommended initial dose of this drug is based on the platelet count. 50,000∼100,000/mm3: 10mg twice daily 100,000∼200,000/mm3: 15mg twice daily >200,000/mm3: 20mg twice daily Polycythemia vera and graft-versus-host disease: 10mg twice daily The dose should be adjusted based on safety and efficacy. Myelofibrosis and polycythemia vera If efficacy is considered inadequate and blood cell counts are adequate, the dose may be increased by up to 5mg twice daily; the maximum dose of this drug is 25mg twice daily. The initial dose should be maintained for the first 4 weeks after starting treatment, and the dose should not be increased more frequently than every 2 weeks thereafter. Treatment should be interrupted if the platelet count is below 50,000/mm3 or the absolute neutrophil count is below 500/mm3. When used to treat polycythemia vera, treatment should be interrupted if hemoglobin is below 8 g/dL. When blood cell counts recover to these levels or higher, treatment may be resumed at 5 mg twice daily, with careful monitoring of blood cell counts and gradual dose escalation. In myelofibrosis, if the platelet count decreases as shown in the following table, dose reduction should be considered to avoid treatment interruption due to thrombocytopenia. Platelet count 100,000/mm3 or more and below 125,000/mm3: For a dose of 25 mg twice daily, the new dose is 20 mg twice daily; for a dose of 20 mg twice daily, the new dose is 15 mg twice daily; for a dose of 15 mg twice daily, the new dose is 15 mg twice daily; for a dose of 10 mg twice daily, the new dose is 10 mg twice daily; for a dose of 5mg twice daily, the new dose is 5 mg twice daily Platelet count 75,000/mm3 or more and below 100,000/mm3: For a dose of 25 mg twice daily, the new dose is 10 mg twice daily; for a dose of 20 mg twice daily, the new dose is 10 mg twice daily; for a dose of 15 mg twice daily, the new dose is 10 mg twice daily; for a dose of 10 mg twice daily, the new dose is 10 mg twice daily; for a dose of 5mg twice daily, the new dose is 5 mg twice daily Platelet count 50,000/mm3 or more and below 75,000/mm3: For a dose of 25 mg twice daily, the new dose is 5 mg twice daily; for a dose of 20 mg twice daily, the new dose is 5 mg twice daily; for a dose of 15 mg twice daily, the new dose is 5 mg twice daily; for a dose of 10 mg twice daily, the new dose is 5 mg twice daily; for a dose of 5mg twice daily, the new dose is 5 mg twice daily Platelet count below 50,000/mm3: Temporarily interrupt treatment for doses of 25 mg twice daily, 20 mg twice daily, 15 mg twice daily, 10 mg twice daily, or 5mg twice daily When used to treat polycythemia vera, dose reduction should be considered if hemoglobin decreases to below 12 g/dL, and dose reduction is recommended if hemoglobin is below 10 g/dL. Hemoglobin 12 g/dL or higher and platelet count 100,000/mm3 or higher: No dose adjustment required Hemoglobin 10 g/dL or higher but below 12 g/dL and platelet count 75,000/mm3 or higher but below 100,000/mm3: Consider dose reduction to prevent treatment interruption due to anemia and thrombocytopenia Hemoglobin 8 g/dL or higher but below 10 g/dL or platelet count 50,000/mm3 or higher but below 75,000/mm3: Reduce to 5mg twice daily; patients already receiving 5mg twice daily should be reduced to 5mg once daily Hemoglobin below 8 g/dL or platelet count below 50,000/mm3: Discontinue treatment Graft-versus-host disease In patients with graft-versus-host disease, dose reduction and temporary interruption may be required if thrombocytopenia, neutropenia, or elevated total bilirubin occurs despite standard supportive care, including growth factors, anti-infective therapy, and transfusions. A one-level dose reduction is recommended (reduce from 10 mg twice daily to 5mg twice daily or from 5mg twice daily to 5mg once daily). Treatment should be discontinued in patients who do not tolerate this drug at a dose of 5mg once daily. Platelet count below 20,000/mm3: Reduce this drug by one dose level. If the platelet count reaches 20,000/mm3 or higher within 7 days, the dose may be increased to the initial dose level; otherwise, maintain the reduced dose. Platelet count below 15,000/mm3: Interrupt treatment with this drug until the platelet count is 20,000/mm3 or higher, then resume treatment at one dose level lower. Absolute neutrophil count (ANC) 500/mm3 or higher and below 750/mm3: Reduce this drug by one dose level. Resume treatment at the initial dose if ANC exceeds 1,000/mm3. Absolute neutrophil count (ANC) below 500/mm3: Interrupt treatment with this drug until ANC exceeds 500/mm3, then resume treatment at one dose level lower. Treatment may be resumed at the initial dose if ANC exceeds 1,000/mm3. Elevated total bilirubin in patients without liver graft-versus-host disease Above 3.0 x ULN and up to 5.0 x ULN: Maintain treatment with this drug at one dose level lower until total bilirubin is 3.0 x ULN or lower. Above 5.0 x ULN and up to 10.0 x ULN: Interrupt treatment with this drug for up to 14 days until total bilirubin is 3.0 x ULN or lower. If total bilirubin is 3.0 x ULN or lower, treatment may be resumed at the current dose. If it is not 3.0 x ULN or lower after 14 days, resume treatment at one dose level lower. Above 10.0 x ULN: Interrupt treatment with this drug until total bilirubin is 3.0 x ULN or lower, then resume treatment at one dose level lower. Elevated total bilirubin in patients with liver graft-versus-host disease Above 3.0 x ULN: Maintain treatment with this drug at one dose level lower until total bilirubin is 3.0 x ULN or lower. Dose adjustment when coadministered with a strong CYP3A4 inhibitor or fluconazole In patients with myelofibrosis and polycythemia vera who receive this drug with a strong CYP3A4 inhibitor, or in patients with myelofibrosis, polycythemia vera, or graft-versus-host disease who receive it with a dual moderate inhibitor of CYP2C9 and CYP3A4 enzymes, such as fluconazole, the total daily dose of this drug should be reduced by approximately 50%. Adjust the dose by reducing the twice-daily dose or, if twice-daily administration is not possible, by reducing the dosing frequency to the corresponding once-daily dose. When this drug is coadministered with fluconazole, fluconazole should not exceed 200mg per day. When this drug is coadministered with a strong CYP3A4 inhibitor or a dual moderate inhibitor of CYP2C9 and CYP3A4 enzymes, hematologic parameters and clinical signs or symptoms of adverse reactions caused by this drug should be monitored more frequently. No dose adjustment is required when this drug is coadministered with a mild or moderate CYP3A4 inhibitor. Patients with renal impairment The recommended initial dose for myelofibrosis in patients with moderate (creatinine clearance 30 mL/min or higher and below 50 mL/min) or severe renal impairment (creatinine clearance below 30 mL/min) is 10mg twice daily. The recommended initial dose for polycythemia vera and graft-versus-host disease in patients with moderate or severe renal impairment is 5mg twice daily. Safety and efficacy should be carefully monitored during treatment with this drug, and additional dose adjustments may be necessary. Data are limited for determining the optimal dose for myelofibrosis in patients with end-stage renal disease (ESRD) requiring hemodialysis. Available results in these patients indicate that the recommended initial dose is a single dose of 15mg for patients with a platelet count of 100,000∼200,000/mm3 and a single dose of 20mg for patients with a platelet count above 200,000/mm3. The dose should be administered only on the day of dialysis, after dialysis, and should not be given more than once daily. Dose adjustments should be made with careful monitoring of safety and efficacy. No data are available on administration to patients receiving peritoneal dialysis or continuous venovenous hemofiltration. The recommended initial dose for polycythemia vera and graft-versus-host disease in patients with ESRD requiring hemodialysis is a single dose of 10mg, administered only on the day of dialysis, after dialysis; safety and efficacy should be carefully monitored. Patients with hepatic impairment The recommended initial dose for myelofibrosis in patients with hepatic impairment should be reduced to 10mg twice daily, and the recommended initial dose for polycythemia vera should be reduced to 5mg twice daily. Subsequent doses should be adjusted with careful monitoring of safety and efficacy. No change to the initial dose is recommended in patients with graft-versus-host disease who have hepatic impairment, including liver graft-versus-host disease. In patients with liver involvement from graft-versus-host disease and total bilirubin levels above 3 x ULN, toxicity and blood counts should be monitored more frequently, and a one-level dose reduction may be considered. No dose adjustment is required in elderly patients.

Child dose

Pediatric patients with myelofibrosis and polycythemia vera: The safety and efficacy of this medication have not been established. Pediatric patients aged 12 years and older with graft-versus-host disease: The dosage of this medication is the same as that for adults. Patients under 12 years of age: The safety and efficacy of this medication have not been established.

This medication may reduce blood cell counts in the blood, so it is essential to check blood cell counts before administration. If platelet or neutrophil counts are too low, administration should be discontinued. Especially in myelofibrosis patients with low platelet counts, thrombocytopenia may occur more easily. Thrombocytopenia, anemia, and neutropenia generally recover after reducing the dose or temporarily discontinuing the medication, but transfusions may be necessary if needed. This medication contains lactose, so it is not to be used in patients with lactose intolerance or related genetic disorders. Blood-related adverse effects such as anemia, thrombocytopenia, and neutropenia may occur frequently. Moreover, non-hematologic adverse effects such as bruising, dizziness, and urinary tract infections are also reported frequently. Regular liver function tests are required as liver function test results may increase. There is a risk of severe infections during treatment, thus patients should be vigilant for signs of infection and receive immediate treatment as symptoms arise. Testing for latent infections such as tuberculosis should also be done prior to starting therapy. It is advisable not to use this medication during pregnancy, and women of childbearing potential should take effective contraception during treatment. Breastfeeding women should consider discontinuing nursing or the medication as this drug can be transmitted through breast milk. Abrupt discontinuation of this medication may lead to a recurrence of myelofibrosis symptoms, so it is recommended to taper the dose gradually when discontinuing. This medication can cause lipid abnormalities such as hypercholesterolemia and hypertriglyceridemia, so regular blood tests are necessary. Patients at risk for cardiovascular disease should be monitored closely before and after taking this medication. As there may be drug interactions, patients taking other medications should consult with their physician or pharmacist, especially regarding potential use with CYP3A4 inhibitors or inducers, as dosage adjustments may be necessary. In the case of overdose, there is no antidote, so immediate hospital attention should be sought for proper care. This medication should be stored out of reach of children, and it is safer not to transfer it to other containers.

• Anemia
• thrombocytopenia
• neutropenia
• bruising
• dizziness
• urinary tract infection
• ALT elevation
• AST elevation
• hypertriglyceridemia
• weight gain

This medication should be stored in a tightly closed container to protect it from air and moisture. The storage temperature should be maintained at room temperature between 1°C and 25°C. This way, the effectiveness and safety of the medication can be well-preserved.

Appearance

Oval-shaped tablet that varies from white to off-white

Package unit

56 tablets (14 tablets/PTP packaging x 4)